Biosensors including surface resonance spectroscopy and semiconductor devices

ABSTRACT

A sensor including a surface plasmon resonance detector with a reservoir for containing a liquid sample. The sensor further includes a sensing metallic film positioned within the reservoir so that at least a majority of a surface of the sensing metallic film is to be in contact with the liquid sample being housed within the reservoir. The sensory also includes a semiconductor device having a contact in electrical communication with the sensing metal containing film that is positioned within the reservoir. The semiconductor device measures the net charges of molecules within the liquid sample within a Debye length from the sensing metallic film.

BACKGROUND

Technical Field

The present disclosure relates generally to sensors for biomoleculesensing, and more particularly to structures and methods for makingmeasurements from a liquid solution including biomolecules.

Description of the Related Art

Bio-molecule sensing is important in healthcare. One example ofbio-molecule sensing is referred to as surface plasmon resonancespectroscopy, generally designated as SPR (surface plasmon resonance).This method is based upon the optical excitation of surface plasmons inthin metal layers. The resonance conditions for the excitation ofsurface plasmons strongly depend on the optical properties of thedielectrics surrounding the metal layer. Hence, it is principallyfeasible to determine the refractive index and the layer thickness ofthin dielectric layers with high precision. SPR-spectroscopy finds anincreasing application in biochemical analysis, since it permits adirect analysis of the interactions between the bio-molecules (forexample, antibody/antigen reactions at or near the sensor surface). Tothis end a reactant (ligand) is immobilized on the metal surface, andthe other reactant (analyte) in solution is passed over the surface. Theinteraction can be directly detected as a change in dielectric constant(refractive index) which can be translated into an increase in layerthickness. There is no marking of the reactants necessary as, forexample, with the radioimmunoassay (RIA) or the enzyme-linkedimmunosorbent assay (ELISA). A drawback that is common to SPR is falsepositives.

SUMMARY

In one aspect, a sensor is provided that includes a surface plasmonresonance detector with a reservoir for containing a liquid sample, anda sensing metallic film positioned within the reservoir so that at leasta majority of a surface of the sensing metallic film is to be in contactwith the liquid sample being housed within the reservoir. The sensorfurther includes a semiconductor device having a contact in electricalcommunication with the sensing metal containing film that is positionedwithin the reservoir. The semiconductor device measures the net chargeswithin the liquid sample within a Debye length from the sensing metallicfilm.

In another aspect, a sensor is provided that includes a bipolar junctiontransistor that includes an emitter region, a base region and acollector region; and a reservoir for housing a liquid solution. Thesensor further includes a metal containing contact that extends from thebase region into the reservoir. The metal containing contact provides asensing surface for measuring at least one of a presence of biomoleculesin a solution and temperature of biomolecules in the solution.

In yet another aspect, a method of measuring a concentration of ions ina solution is provided that includes providing electrical communicationbetween a base region of a bipolar junction transistor (BJT) and thesolution of ions being measured. The electrical communication betweenthe BJT and the solution of ion being measured is through an extensionof a metal containing contact from the base region of the BJT to thesolution of ions, in which portion of the metal containing contactimmersed in the solution of ions provides a sensing surface. Current ismeasured from a collector region of the BJT, wherein changes in currentbeing measured from the collector denotes changes in concentration ofions in the solution of ions.

BRIEF DESCRIPTION OF DRAWINGS

The disclosure will provide details in the following description ofpreferred embodiments with reference to the following figures wherein:

FIG. 1A is a side cross-sectional view of a bipolar junction transistor(BJT) including a metal containing contact from the base region of theBJT that extends into a reservoir for detecting biomolecules, inaccordance with one embodiment of the present disclosure.

FIG. 1B is a top down view depicting a base contact that provides thesensing surface for the BJT molecular sensor that is present within theperimeter of the base region, in accordance with one embodiment of thepresent disclosure.

FIG. 1C is a top down view depicting a base contact that provides thesensing surface for the BJT molecular sensor that extends outside theperimeter of the base region, in accordance with one embodiment of thepresent disclosure.

FIG. 2 is a side cross-sectional view of a BJT molecular sensor having alateral orientation, in accordance with one embodiment of the presentdisclosure.

FIG. 3 is a side cross-sectional view of a BJT molecular sensor having avertical orientation, in accordance with one embodiment of the presentdisclosure.

FIG. 4A is a plot of collector current curves measured in aqueoussolution with different NaCl concentration using a PNP BJT sensor withsilver chloride (AgCl) as the sensing surface, in accordance with oneembodiment of the present disclosure.

FIG. 4B is a plot obtained from the data shown in FIG. 4A for PNPsensor. In plot FIG. 4B, the y-axis is the emitter voltage (V_(e)) valueat which the collector current (I_(c))=10⁻⁷ A corresponding to differentNaCl concentrations of the solution. The plot shows the dependence ofthe sensing signal as a function of Cl⁻ concentration of the solution.

FIG. 4C shows the dependence of the sensing current I_(c) measured at afixed emitter voltage (V_(e))=0.5V as a function of Cl⁻ concentration inthe solution using PNP BJT sensor.

FIG. 5A is a plot of current curves measured from an NPN BJT molecularsensor with silver chloride (AgCl) as the sensing surface. The collectorcurrent (I_(C)) is measured as function of applied emitter voltage(V_(e)) for different NaCl concentrations of the solution, in accordancewith one embodiment of the present disclosure.

FIG. 5B is a plot obtained from the data shown in FIG. 5A for NPN BJTmolecular sensor. In plot FIG. 5B, the y-axis is the emitter voltage(V_(e)) value at which the collector current (I_(c))=10⁻⁷ Acorresponding to different NaCl concentrations of the solution. The plotshows the dependence of the sensing signal as a function of Cl⁻concentration of the solution.

FIG. 5C shows the dependence of the sensing current (I_(c)) measured ata fixed emitter voltage V_(e)=−0.3V as a function of Cl⁻ concentrationin the solution using NPN BJT molecular sensor.

FIG. 6 is a plot depicting temperatures inferred from a NPN BJT sensor.The collector current (I_(C)) is measured as a function of emittervoltage (V_(e)) at three different temperatures. At each temperature,the current is observed to have an exponential dependence on the emittervoltage (Ve) with an exponent=1/kT, where k is Boltzmann constant and Tis the temperature in Kelvin. Hence, the measured exponent valueprovides measure of the temperature.

FIG. 7A is a side cross-sectional view depicting a combined surfaceplasmon resonance (SPR) and extended gate structure field effecttransistor (FET) biomolecule sensor including a smooth metal containingsensing surface, in accordance with one embodiment of the presentdisclosure.

FIG. 7B is a side cross-sectional view depicting a combined surfaceplasmon resonance (SPR) and bipolar junction transistor (BJT) having anextended base contact biomolecule sensor including a smooth metalcontaining sensing surface, in accordance with one embodiment of thepresent disclosure.

FIG. 8A is a side cross-sectional view depicting a combined surfaceplasmon resonance (SPR) and extended gate structure field effecttransistor (FET) biomolecule sensor including a grated metal containingsensing surface, in accordance with one embodiment of the presentdisclosure.

FIG. 8B is a side cross-sectional view depicting a combined surfaceplasmon resonance (SPR) and bipolar junction transistor (BJT) having anextended base contact biomolecule sensor including a grated metalcontaining sensing surface, in accordance with one embodiment of thepresent disclosure.

FIG. 9 is a plot of the drain current (Id) measured as a function of thegate voltage (Vg) taken from a field effect transistor (FET) biomoleculesensor in an arrangement with an SPR device as depicted in FIGS. 7A-8B,in accordance with the present disclosure.

FIG. 10 is a top down view depicting a sensing surface for the combinedSPR and semiconductor device biomolecule sensor that is depicted inFIGS. 7A-8B, in accordance with the present disclosure.

DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS

Detailed embodiments of the claimed structures and methods are disclosedherein; however, it is to be understood that the disclosed embodimentsare merely illustrative of the claimed structures and methods that maybe embodied in various forms. In addition, each of the examples given inconnection with the various embodiments are intended to be illustrative,and not restrictive. Further, the figures are not necessarily to scale,some features may be exaggerated to show details of particularcomponents. Therefore, specific structural and functional detailsdisclosed herein are not to be interpreted as limiting, but merely as arepresentative basis for teaching one skilled in the art to variouslyemploy the methods and structures of the present disclosure. Forpurposes of the description hereinafter, the terms “upper”, “lower”,“right”, “left”, “vertical”, “horizontal”, “top”, “bottom”, andderivatives thereof shall relate to the embodiments of the disclosure,as it is oriented in the drawing figures. The term “positioned on” meansthat a first element, such as a first structure, is present on a secondelement, such as a second structure, wherein intervening elements, suchas an interface structure, e.g. interface layer, may be present betweenthe first element and the second element. The term “direct contact”means that a first element, such as a first structure, and a secondelement, such as a second structure, are connected without anyintermediary conducting, insulating or semiconductor layers at theinterface of the two elements.

In some embodiments, the methods and structures disclosed herein providea biomolecule sensor provided by a bipolar junction transistor (BJT). Asensor is disclosed herein that provides for label free detection, i.e.,there is no fluorescence or radioactive tag needed to be attached to thetarget molecule before it can be detected, of bio-molecules. The term“bipolar junction transistor” denotes a type of transistor made of threeregions of semiconductor materials each having an inherent electricalcharge, i.e., conductivity, such as n-type or p-type conductivity. Eachregion has been treated, e.g., doped, so that the layer in the middle(called the base region) has a first conductivity type, while the layersaround it, i.e., the emitter region and the collector region) have asecond conductivity type opposite to the first conductivity type. Abipolar junction transistor with an n-type base is designated PNP, andone with a p-type base is designated NPN. When subjected to currentflow, the base acts like a gate, enhancing or inhibiting the currentflow from the emitter to the collector. The bio-molecule sensor of thepresent disclosure also includes a reservoir for housing the liquidsolution from which at least a concentration of molecules, e.g., ions,is measured. A sensing surface is immersed in the liquid solution and isin electrical communication with the base region of the BJT. Forexample, at least 75% of the sensing element is in contact with theliquid solution that is within the reservoir. In some embodiments, thesensing surface is in electrical contact through an electricallyconductive extension from the base region. The methods and structures ofthe present disclosure directed to the bio-molecule sensor composed of aBJT are now described in more detail with reference to FIGS. 1-10.

FIG. 1A depicts one embodiment of a bipolar junction transistor (BJT)100 including a metal containing contact 30 from the base region 15 ofthe BJT 100 that extends into electrical communication with a reservoir50 for detecting biomolecules within a liquid solution being containedwithin the reservoir 50. The BJT 100 typically includes an emitterregion 10 and a collector region 20 on opposing sides of the base region15. The emitter region 10 and the collector region 20 have an oppositeconductivity type as the base region 15. The term “conductivity type” asused herein denotes whether a region has a p-type conductivity or ann-type conductivity. As used herein, “p-type” refers to the addition ofimpurities to a semiconductor that creates deficiencies of valenceelectrons. In a type IV semiconductor material, such as germanium orsilicon, examples of p-type dopants include but are not limited toboron, aluminum, gallium and indium. As used herein, “n-type” refers tothe addition of impurities that contributes free electrons to asemiconductor. In a semiconductor material composed of a type IVsemiconductor, such as germanium or silicon, examples of n-type dopants,i.e., impurities, include but are not limited to, antimony, arsenic andphosphorous.

In the embodiment that is depicted in FIG. 1A, the emitter region 10,base region 15 and collector region 20 are formed in the semiconductoron insulator (SOI) layer 4 of a semiconductor on insulator (SOI)substrate 5. In some embodiments, the SOI layer 4 that provides the sitefor the emitter region 10, the base region 15 and the collector region20 is composed of a silicon-containing material. Examples of siliconcontaining materials that are suitable for SOI layer 4 that contains theemitter region 10, the base region 15 and the collector region 20include silicon (Si), silicon germanium (SiGe), silicon germanium dopedwith carbon (SiGe:C), silicon carbon (Si:C), and combinations thereof.In other embodiments, the SOI layer 4 may be principally composed ofanother type IV semiconductor, such as germanium (Ge). In yet otherembodiments, the SOI layer 4 may be composed of a compoundsemiconductors, such as III-V semiconductors. It is noted that the abovelist of semiconductor materials is provided for illustrative purposesonly, and is not an exhaustive list, as other semiconductor materialsmay be suitable for the semiconductor material of the emitter region 10,base region 15, and the collector region 20 of the BJT 100. Thesemiconductor material that provides the emitter region 10, base region15 and the collector region 20 may have a single crystal crystallinestructure, multi-crystalline or poly-crystalline crystal structure. Thedopant that dictates the conductivity type of the emitter region 10,base region 15 and the collector region 20 may have introduced via ionimplantation or in situ doping. In situ doping is the doping of asemiconductor material as it is formed. The SOI substrate 5 may alsoinclude a buried oxide layer 2 and base semiconductor layer 1.

Referring to FIG. 1A, in some embodiments, an electrically conductivecontact 30, 35, 40 may be formed to each of the emitter region 10, thebase region 15 and the collector region 20. The electrically conductivecontact 30 that is present in electrical communication with the baseregion 15 may provide the sensing surface of the bio-molecule sensor100. As used herein, the term “electrical communication” means that afirst structure or material can conduct electricity, i.e., iselectrically conductive, to a second structure or material. The term“electrically conductive” as used herein denotes a material typicallyhaving a room temperature conductivity of greater than 10⁷ Siemens/m. Insome embodiments, the material of the electrically conductive contact30, 35, 40 is a metal containing material. Examples of electricallyconductive metals that are suitable for the electrically conductivecontacts 30, 35, 40 include silver (Ag), gold (Au), tungsten (W), nickel(Ni), titanium (Ti), molybdenum (Mo), tantalum (Ta), copper (Cu),platinum (Pt), ruthenium (Ru), iridium (Jr), rhodium (Rh), and rhenium(Re), and alloys that include at least one of the aforementionedconductive elemental metals. The electrically conductive contacts 30,35, 40 may also be metal nitrides, such as titanium nitride (TiN),tantalum nitride (TaN), tungsten nitride (WN), and a combinationthereof. In yet another embodiment, the electrically conductive contacts30, 35, 40 may be composed of a metal semiconductor alloy. For example,the electrically conductive contacts 30, 35, 40 can be composed of asilicide, which is an alloy of silicon and a metal element. Examples ofsilicides that are suitable for the electrically conductive contacts 30,35, 40 include nickel monosilicide, nickel disilicide, cobalt silicide,tungsten silicide and combinations thereof. It is noted that the aboveexamples of compositions for the electrically conductive contacts 30,35, 40 are provided for illustrative purposes only, and are not intendedto limit the present disclosure. In some embodiments, the electricallyconductive contact 30 to the base region 15 of the BJT should have aresistance of less than 1 ohm, as functionalized to provide the sensingsurface for the BJT biomolecule.

The electrically conductive contacts 30, 35, 40 may be formed usingdeposition methods in combination with etch processes or block masks toselect which regions of the SOI layer that the electrically conductivecontacts 30, 35, 40 are formed on. For example, the electricallyconductive contact 30 to the emitter region 10 is separated from each ofthe electrically conductive contacts 30, 40 to the base region 15 andthe collector region 20, respectively. Further, the electricallyconductive contact 40 to the collector region 20 is separated from theelectrically conductive contacts 35, 30 to the emitter and base regions10, 15, respectively. The electrically conductive contact 30 to the baseregion 15 is separated from the electrically conductive contacts 35, 40to the emitter region 10 and the collector region 20. In someembodiments, to ensure electrical isolation between the electricallyconductive contacts 35, 40 to the emitter and collector region 10, 20and the electrically conductive contact 30 to the base region 15, adielectric spacer 25 is formed on the interface between the emitterregion 10 and the base region 15, as well as the interface between thebase region 15 and the collector region 20. The dielectric spacer 25 ispositioned to separate the electrically conductive contact 30 to thebase region 15 from the electrically conductive contacts 35, 40 to theemitter and collector regions 10, 20. The dielectric spacer 25 may becomposed of any dielectric material, such as an oxide, nitride oroxynitride material. For example, the dielectric spacer 25 may becomposed of silicon oxide (SiO₂), silicon nitride (Si₃N₄) or siliconoxynitride.

Still referring to FIG. 1A, an interlevel dielectric 45 may be presenton the upper surface of the SOI layer 4 including the electricallyconductive contacts 30, 35, 40 and the dielectric spacer 25. Openingsmay be present through the interlevel dielectric to provide a reservoir50 to for containing the liquid suspension to be measured by the sensingsurface of the electrically conductive contact 30 to the base region 15.The electrically conductive contact 30 is the sensing surface connectedto the base of the bipolar junction transistor (BJT). A voltage isapplied to the solution using a reference electrode 60, and this appliedvoltage is referred as V_(ref). Openings may also be provided to providemetal studs 55 to the electrically conductive contacts 35, 40 to theemitter region 10 and the collector region 20. The metal stud 55 to theelectrically conductive contact 35 to the emitter region 10 is thestructure through which the emitter voltage (Ve) is applied to thebipolar junction transistor (BJT). The metal stud 55 to the electricallyconductive contact 40 to the collector region 20 is the structurethrough which the collector current (Ic) is measured.

It is noted that the embodiment depicted in FIG. 1A is only oneembodiment of the present disclosure, and that it is not necessary thatthe reservoir 50 be embedded within an interlevel dielectric. Thereservoir 50 may be provided by any vessel that can contain a liquidsuspension, in which the sensing surface to the electrically conductivecontact 30 to the base region 15 may be positioned. For example, thereservoir 50 may be a glass or plastic container. In some embodiments,the geometry of the reservoir 50 is selected so that the base of thereservoir 50 has an area ranging from 1 μm² to 1 mm². In other examples,the reservoir 50 is selected so that the base of the reservoir 50 has anarea ranging from 1.25 μm² to 0.75 mm². It Is noted that the reservoir50 can have any geometry and size, so long as the reservoir 50 cancontain the sensing surface.

The electrically conductive contact 30 to the base region 15 of the BJT100 provides the sensing surface of the bio-molecule sensor. Thesemiconductor device, e.g., BJT 100, measures the net charges within theliquid sample within a Debye length from the sensing surface, e.g.,sensing metallic film. Typically, the Debye length decreases withincreasing ion concentration in the solution with square rootdependence. The Debye length can be important because the chargesoutside this length as measured from the sensing surface cannot beelectrically detected. For example, when the electrically conductivecontact 30 to the base region 15 is composed of silver chloride (AgCl),the BJT bio-molecule sensor 100 may be employed to detect the presenceof Chlorine (Cl⁻) ions in a liquid solution. The silver chloride (AgCl)of the sensing surface may be the base material of the electricallyconductive contact 30, or may be a coating to functionalize theelectrically conductive contact 30 for detecting the presence ofchlorine (Cl—) ions in a liquid solution. In another embodiment, theelectrically conductive contact 30 to the base region 15 is composed oftitanium nitride (TiN), wherein the titanium nitride (TiN) sensingsurface can detect the pH of a liquid solution, the pH of the liquidsolution then being correlated to the concentration of protons (H⁺) inthe liquid solution. In yet another embodiment, the surface of theelectrically conductive contact 30 to the base region 15 is chemicallymodified with proteins and/or ions for binding with proteins and/or ionsin the liquid solution. For example, to detect strepavidin protein, thesensing surface can be coated with biotin, because biotin specificallybinds the streptavidin protein.

In each of the above examples, during measurement of the liquidsuspension by the BJT biomolecule sensor, charged bio molecules, e.g.,chlorine (Cl⁻) and protons (H⁺), adhere to the sensing surface of theelectrically conductive contact 30 to the base region 15, which changesthe electrically properties of the biomolecule sensor, such as thecollector current (Ic).

In some embodiments, only the sensing surface of the electricallyconductive contact 30 to the base region is in contact with, e.g.,immersed in, the liquid solution that is contained within the reservoir50 from which the measurements are taken. In some embodiments, toprovide that only the sensing surface of the electrically conductivecontact 30 to the base region 15 is in contact with the liquid solution,the reservoir 50 is formed directly atop the sensing surface, theelectrically conductive contact 30 and the base region 15, as depictedin FIG. 1B. FIG. 1B depicts an embodiment of the present disclosure inwhich an entirety of the electrically conductive contact 30 provides thesensing surface of the BJT biomolecule sensor 100. In the embodimentdepicted in FIG. 1B, the reservoir 50, the electrically conductivecontact 30, and the sensing surface are directly atop and aligned withthe perimeter of the base region 15. In other embodiments, theelectrically conductive contact includes an extension portion 30 a. Theextension portion 30 a is the portion of the electrically conductivecontact 30 that is not present overlying (within the perimeter) of thebase region 15. FIG. 1C depicts one embodiment of an electricallyconductive contact 30 having an extension portion 30 a. In someembodiments, the extension portion 30 a of the electrically conductivecontact 30 is treated to provide the sensing surface, wherein thesensing surface, i.e., extension portion 30 a, of the electricallyconductive contact 30 is the only portion of the electrically conductivecontact 30 that is present immersed within the liquid suspension, asdepicted in FIGS. 2 and 3.

As depicted in FIGS. 1A, 1B, 1C and 2, the BJT biomolecule sensor 100may have a lateral orientation. By having a “lateral orientation” it ismeant that the emitter region 10, base region 15 and collector region 20are present on a substrate and are orientated left to right, or right toleft, as depicted in FIGS. 1A, 1B, 1C and 2. The BJT biomolecule sensor100 may also include a vertical orientation. By “vertical orientation”it is meant that the emitter region 10, base region 15 and collectorregion 20 are orientated in a stacked arrangement, e.g., from top tobottom, on a surface of a substrate, as depicted in FIG. 3.

FIG. 2 depicts one embodiment of a lateral orientation BJT biomoleculesensor 100 having an extension portion 30 a that provides the sensingsurface of the electrically conductive contact 30 to the base region 15that is immersed within the liquid solution housed by the reservoir 50.As depicted in FIG. 2, in some embodiments, the sensing surface portion,i.e., extension portion 30 a, of the electrically conductive contact 30is the only portion of the electrically conductive contact 30 that isimmersed within the liquid solution. In this example, the reservoir 50is remotely positioned from the base region 15 of the BJT moleculesensor 100. Although the sensing surface is depicted as being anextension of the electrically conductive contact 30 to the base region15, embodiments have been contemplated in which the sensing surface isphysically separated from the electrically conductive contact 30 to thebase region 15 but in electrical communication to the electricallyconductive contact 30 to the base region 15 through an electricallyconductive wire. A reference electrode 60 is also present immersed inthe liquid suspension being contained by the reservoir 50.

FIG. 3 depicts one embodiment of a vertical orientation BJT biomoleculesensor 100. Similar to the lateral orientation BJT biomolecule sensorthat is depicted in FIG. 2, the sensing surface portion, i.e., extensionportion 30 a, of the electrically conductive contact 30 to the baseregion 15 of the vertically orientation BJT biomolecule sensor 100 isthe only portion of the electrically conductive contact 30 that isimmersed within the liquid solution. Also similar to the lateralorientation BJT biomolecule sensor, embodiments of the verticalorientation BJT sensor may include a sensing surface that is physicallyseparated from the electrically conductive contact 30 to the base region15, but in electrical communication to the electrically conductivecontact 30 to the base region 15 through an electrically conductivewire. A reference electrode 60 may also be present immersed in theliquid suspension being contained by the reservoir 50.

FIGS. 4A-4C illustrate the electrical performance of a PNP BJT molecularsensor for measuring a concentration of chloride (Cl—) ions within aliquid solution using a sensing surface that is composed of silverchloride (AgCl). FIG. 4A is a plot of collector current (Abs (Ic) (A))as a function of a difference of voltage ((V_(e)−V_(re)f)(V)) betweenthe voltage that is applied to the emitter (Ve) and the referencevoltage (V_(ref)). The reference voltage (V_(ref)) is the voltageapplied to the reference electrode 60 that is depicted in FIGS. 2 and 3.The liquid solution being measured in FIG. 4A is composed of sodiumchloride (NaCl). The plot identified by reference number 61 is a 0.1 mMconcentration of sodium chloride (NaCl) in a pH buffer of 4. The plotidentified by reference number 62 is a 1 mM concentration of sodiumchloride (NaCl) in water. The plot identified by reference number 63 isa 10 mM concentration of sodium chloride (NaCl) in a pH buffer of 4. Theplot identified by reference number 64 is a 100 mM concentration ofsodium chloride (NaCl) in a pH buffer of 4. The plot identified byreference number 65 is a 1000 mM concentration of sodium chloride (NaCl)in a pH buffer of 4. As illustrated by the plots included in FIG. 4A, asthe concentration of sodium chloride (NaCl) is increased, the voltageneeded to achieve a given collector current of the PNP BJT molecularsensor decreases. Specifically, a shift in the collector current curvesof approximately 48 mV/decade was measured, as plotted in FIG. 4B. Inthe plot depicted in FIG. 4B, the collector voltage (Vc) was equal to−0.7 V and the reference voltage (Vref) was equal to 0 V. The shift isto the left as indicated by the arrow 66 in FIG. 4A with increasingchloride (Cl⁻) concentration. FIG. 4C illustrates the dependence of thesensing current (Ic) measured at a fixed emitter voltage (Ve), e.g.,0.5V, on the chloride ion concentration in the solution for a PNP BJTmolecular sensor.

The subthreshold swing (SS), i.e., the slope of the semi-log plot ofcurrent versus voltage, is approximately 60 mV/decade at roomtemperature, which is smaller than the subthreshold swing of fieldeffect transistors (FETs), which provide another type of biomoleculesensor that is less sensitive than the BJT biomolecule sensors that aredisclosed herein.

FIGS. 5A-5C illustrate the electrical performance of a NPN BJT molecularsensor for measuring a concentration of chloride (Cl⁻) ions within aliquid solution using a sensing surface that is composed of silverchloride (AgCl). The NPN BJT molecular sensor illustrates that an NPNBJT molecular sensor will display electrical performance having asubstantially inverse relationship to the PNP BJT molecular sensor thatprovided the data plotted in FIGS. 4A-4C. The liquid solution thatprovided that data depicted in FIGS. 4A-4C is similar to the liquidsolution that provides the data in FIGS. 5A-5C. The plot identified byreference number 71 is a 0.1 mM concentration of sodium chloride (NaCl)in a pH buffer of 4. The plot identified by reference number 72 is a 1mM concentration of sodium chloride (NaCl) in water. The plot identifiedby reference number 73 is a 10 mM concentration of sodium chloride(NaCl) in a pH buffer of 4. The plot identified by reference number 74is a 100 mM concentration of sodium chloride (NaCl) in a pH buffer of 4.The plot identified by reference number 75 is a 1000 mM concentration ofsodium chloride (NaCl) in a pH buffer of 4. As illustrated by the plotsincluded in FIG. 5A, as the concentration of sodium chloride (NaCl) isincreased, the voltage needed to achieve a given collector current ofthe NPN BJT shifts to the left. Specifically, a shift in the collectorcurrent curves of approximately −46 mV/decade was measured, as plottedin FIG. 5B. In the plot depicted in FIG. 5B, the collector voltage (Vc)was equal to −0.7 V and the reference voltage (Vref) was equal to 0 V.The shift is to the left as indicated by the arrow 76 in FIG. 5A withincreasing chloride (Cl⁻) concentration. FIG. 5C illustrates thatdependence of the sensing current (Ic) measured at a fixed emittervoltage (Ve)=−0.3V on the chloride ion concentration in the solution foran NPN BJT sensor.

In some embodiments, the NPN and PNP BJT molecular sensors that employ asensing surface that is composed of titanium nitride (TiN) can alsomeasure the temperature of the liquid solution. More specifically, thetemperature can be correlated to changes in the slope of a semi-log plotof current versus using the current taken from the collector region 20of the BJT molecular sensor. FIG. 6 depicts a semi-log plot of currentversus voltage curves taken from an NPN BJT biomolecule sensor in whichthe Y-axis is a current measured from the collector region (Abs (Ic)(A))and the X-axis is a measurement of a difference of voltage((V_(e)−V_(ref))(V)) between the voltage that is applied to the emitter(V_(e)) and the reference voltage (V_(ref)) applied to the solution. Inthe example that is depicted in FIG. 6, the collector current (Ic)curves are measured at three different temperatures. The plot of thecollector current (Ic) identified by reference number 81 was taken froma liquid solution having a temperature of about 65° C. The slope of theplot identified by reference number 81 was approximately 66.4 mV/decade.The plot of the collector current (Ic) identified by reference number 82was taken from a liquid solution having a temperature of about 45° C.The slope of the plot identified by reference number 81 wasapproximately 62.7 mV/decade. The plot of the collector current (Ic)identified by reference number 83 was taken from a liquid solutionhaving a temperature of about 25° C. The slope of the plot identified byreference number 81 was approximately 59.7 mV/decade. As indicated bythe plots including in FIG. 6, the slope of the collector current curvesbecomes shallower with increasing temperature. The following equationwas used to extract the temperature from the data recorded in FIG. 6:Ic=Io*exp((Vref−Ve)/kT)  Equation 1

wherein Io is a constant independent of applied emitter (Ve) andreference (Vref) voltages (ref: “Physics of Bipolar Devices” by SM Sze,(John Wiley & Sons)), T is the temperature and k is a Boltzmannconstant. In view of Equation 1, when the collector current is plottedin a log scale, there is an inverse relationship between the slope ofthe collector current (Ic) measured from the BJT measuring theconcentration of the liquid suspension that is in electricalcommunication to the base region 15 of the BJT through a sensing surfacecomposed of TiN and the temperature of the liquid. This relationshipbetween collector current and temperature is the same for both NPN andPNP BJTs. Therefore, in some embodiments, the NPN and PNP BJTbiomolecule sensors can provide simultaneous measurement of biomoleculeconcentration within a liquid suspension and a measurement of thetemperature of the liquid suspension.

It is noted that the above example of NPN and PNP BJT biomoleculesensors including a sensing surface composed of silver chloride (AgCl)is provided for illustrative purposes only, and is not intended to limitthe present disclosure. For example, other materials that maysimultaneously provide for measurements of biomolecule concentration andtemperature may include Au, Ag, TiN, TaN, AgCl, biotin coated gold,aptamer coated gold and antibody protein coated gold or titaniumnitride.

In another example, the sensing surface of the electrically conductivecontact 30 to the base region 15 of the BJT biomolecule sensor may becomposed of titanium nitride (TiN), wherein the titanium nitride sensingsurface measures the pH of the liquid suspension that is containedwithin the reservoir is correlated to a concentration of protons (H+)through the following equation:pH=−log 10[H+]  Equation 2

The temperature of the liquid suspension may also be measured using atitanium nitride (TiN) sensing surface.

In another example, when the sensing surface of the BJT isfunctionalized with biotin (C₁₀H₁₆N₂O₃S) in order to detect streptavidinprotein and the BJT is an NPN transistor, the collector current (Ic),i.e., Ic can increase or decrease depending on the pH of the solution,with increasing concentration of strepavidin protein within the liquidsolution being contained in the reservoir 50. In another example, whenthe sensing surface of the BJT is functionalized with biotin(C₁₀H₁₆N₂O₃S) in order to detect streptavidin protein and the BJT is anPNP transistor, the collector current (Ic) changes, i.e., Ic canincrease or decrease depending on the pH of the solution, withincreasing concentration of strepavidin protein within the liquidsolution being contained in the reservoir 50.

In some embodiments, the BJT biomolecule sensor can be used in a methodof measuring concentration of ions in a solution that includes providinga solution of ions, and providing electrical communication between abase region 15 of a bipolar junction transistor through an extension ofa metal containing contact from the base to the solution of ions, theportion of the metal containing contact immersed in the solution of ionsbeing a sensing surface; and measuring current from a collector region20 of the bipolar junction transistor, wherein changes in current beingmeasured from the collector region 20 denotes changes in concentrationof ions in the solution of ions. In some embodiments, to measure thecurrent from the collector region 20, voltage (Ve) is applied to theemitter region 10 through the metal stud 55 to the electricallyconductive contact 35 to the emitter region 10. The voltage (V_(ref)) isapplied to the solution using a reference electrode immersed in thesolution. The voltage (Ve) that is applied to the emitter region 10typically ranges from −2 Volts to 2 Volts. In some embodiments, thevoltage (Ve) that is applied to the emitter region 10 may range from 0Volts to 1 Volts for PNP BJT sensors and 0 to −1 V for NPN BJT sensors.During the measurement of the collector current (Ic), a referenceelectrode 60 is also present in the reservoir 50 that is containing theliquid solution being measured. The voltage (V_(ref)) applied to thereference electrode 60 is some examples may be 0 volts, but othervoltages for the reference voltage have been considered.

In another aspect, a combined semiconductor device and surface plasmonresonance spectroscopy (SPR) based bio-sensor is provided. Since twodisparate sensing methods (optical/electrical) are simultaneouslysensing the same molecules, the probability for detecting of a falsepositive is reduced. The semiconductor device may be a BJT, as describedwith reference to FIGS. 1-6, or may be a field effect transistor (FET).The semiconductor device may detect change in the charge density nearthe sensing surface, which can be correlated to a concentration ofbiomolecules. SPR is an optical sensing method which detects moleculesby measuring change in the refractive index at the interface of thereflecting surface, such as gold. Surface plasmon resonance (SPR) is thecollective oscillation of electrons in a solid stimulated by incidentlight. The resonance condition is established when the frequency oflight photons matches the natural frequency of surface electronsoscillating against the restoring force of positive nuclei. SPR may beused to determine refractive index of a coating, coating thickness,surface density of adsorbed species etc. from a concentration ofbiomolecules from a testing sample.

Referring to FIGS. 7A-8B, in some embodiments, the SPR detectortypically includes a light source 85, a reflective surface 90 that willsupport a surface plasmon, a spectrometer 95 (usually a CCD detector),and a polarizer 105. In the embodiments depicted in FIGS. 7A and 7B, theliquid suspension 111 from which the biomolecule measurements are madeare in contact with a sensing surface 112 of opposite the surface of thereflective surface 90 that the light from the light source 85 isincident. In the embodiments depicted in FIGS. 7A and 7B, the light fromthe light source 85 travels through a prism 110 and glass surface 113,as well as traveling through the liquid suspension 111, into contactwith the reflective surface 90. The incident light does not actuallypass through the solution before contacting the reflecting surface. Theevanescent wave from the light extends some distance into the analytesolution. Following contact with the reflective surface 90, thereflected light travels through the polarizer 105 into the detector 95.In the embodiments depicted in FIGS. 8A and 8B, the light from the lightsource 85 travels through a glass surface 113 and the liquid suspension111 from which the bianalyte contacts a grated reflective surface 90.Following contact with the grated reflective surface 90, the reflectedlight travels through the polarizer 105 into the spectrometer 95. Thelight source 85 can be a broad band source, but is typically a laser.For example, the light source 85 may be composed of light at differentwavelengths, e.g., from 360 nm to 2000 nm. The spectrometer 95(spectrophotometer, spectrograph or spectroscope) is an instrument usedto measure properties of light over a specific portion of theelectromagnetic spectrum.

SPR sensors are thin film refractometers that measure changes in therefractive index occurring at the metal surface, i.e., reflectivesurface 90, supporting a surface plasmon. A surface plasmon excited bylight wave propagates along the metal film, i.e., reflective surface 90,and its evanescent field probes the medium, i.e., liquid containingsample 111, that is in contact with the reflective surface 90. A changein the reflective index of the dielectric at or near the interface givesrise to a change in the propagation constant of the surface plasmon,which through a coupling condition alters the characteristics of thelight wave coupled to the surface plasmon (e.g., coupling angle,coupling wavelength, intensity phase). For this reason, the light waveis modulated by the surface plasmon is measured, SPR sensors areclassified as sensors with angular, wavelength, intensity or phasemodulation, each of which are suitable for use with the SPR sensordisclosed herein. In the embodiments that are depicted in FIGS. 7A and7B, a prism coupler 110 is employed to couple light to a plasmonsurface. Embodiments employing the prism coupler 110 may employ any typeof modulation described above. In the embodiments depicted in FIGS. 8Aand 8B, a light excites plasmons via a grating coupler provided by agrated reflective surface 90.

In some embodiments, SPR affinity biosensors are sensing devices whichinclude a biorecognition element that recognizes and is able to interactwith a selected analyte causing a shift in the reflectance minimum,thereby translating the binding event into an output signal. Thebiorecognition elements are immobilized in the proximity of the surfaceof a metal film, i.e., reflective surface 90, supporting a surfaceplasmon. Analyte molecules in a liquid sample 111 in contact with theSPR sensor bind to the biorecognition elements, producing an increase inthe refractive index at the sensor surface which is optically measured.The change in refractive index produced by the capture of biomoleculesdepends on the concentration of analyte molecules at the sensor surface,i.e., reflective surface 90, and the properties of the molecules. Insome embodiments, if the binding occurs within a thin layer at thesensor surface of thickness h, the sensor response is proportional tothe binding-induced refractive index charge which can be expressed as:Δn=(dn/dc)(Γ/h)  Equation 3

wherein (dn/dc) denotes refractive index increment of the analytemolecules and F denotes the surface concentration in mass/area.

To provide for a combined biomolecule sensor, the reflective surface 90for the SPR provides the sensing surface for the semiconductor device aswell, which provides a second biomolecule sensor. In the example that isdepicted in FIGS. 7A and 8A, the semiconductor device is a field effecttransistor (FET) 200. A field effect transistor (FET) 200 is asemiconductor device in which output current, i.e., source-draincurrent, is controlled by the voltage applied to a gate structure 210 tothe semiconductor device. A field effect transistor has three terminals,i.e., gate structure 210, source region 211 and drain region 212. A“gate structure” means a structure used to control output current (i.e.,flow of carriers in the channel) of a semiconducting device throughelectrical or magnetic fields. The gate structure 210 typically includesat least one gate dielectric 208 on the channel region of the device,and at least one gate conductor 209 on the at least one gate dielectric208. As used herein, the term “channel” is the region underlying thegate structure 210 and between the source region 211 and drain region212 of a semiconductor device that becomes conductive when thesemiconductor device is turned on. As used herein, the term “drain”means a doped region in semiconductor device located at the end of thechannel, in which carriers are flowing out of the transistor through thedrain. As used herein, the term “source” is a doped region in thesemiconductor device, in which majority carriers are flowing into thechannel. As indicated above, the gate structure 200 of the FET isattached to the reflective surface 90 for the SPR, which provides thesensing surface 112 of the FET sensor. In some embodiments, thesemiconductor device, e.g., FET sensor, measures the net charges ofions/molecules within the liquid sample within a Debye length from thesensing surface, e.g., sensing metallic film. In some examples, thesensing surface of the FET sensor may be a gold (Au) containing film,such as a gold (Au) film. In other embodiments, the reflective surface90 for the SPR, which provides the sensing surface for the FET, may becomposed of silver (Ag), such as a silver (Ag) metal film or a silverchloride (AgCl) film. Silver chloride (AgCl) alone typically does notsupport a surface plasmon wave, but silver chloride (AgCl) mixed withsilver (Ag) nanoparticles will. The matter supporting the surfaceplasmon wave is a free electron species, such as various conductingmetals. The metal could have a coating but it must be thin since itneeds to be penetrated by the evanescent wave to interrogate thesolution interface.

In some embodiments, in which the semiconductor device was a fieldeffect transistor, the gate structure 210 is in electrical communicationto the reflective surface 90 of the SPR through an extended portion 215of the gate conductor 209 for the gate structure 210, as depicted inFIGS. 7A and 8A. The gate structure 210 including the extended gateportion 215 may be referred to as a FET having an extended gate. Inanother embodiment, in which the semiconductor device a FET, the FET isin electrical communication to the reflective surface 90 of SPR throughwire bonding between the gate structure 210 and the reflective surface90.

As the sensing surface 112 for the FET, the reflective surface 90 of theSPR may be composed of silver chloride (AgCl) so that the FETbiomolecule sensor may be employed to detect the presence of Chlorine(Cl⁻) ions in a liquid solution. The silver chloride (AgCl) of thesensing surface for the FET, i.e., reflective surface 90 of the SPR, maybe a base material, or may be a coating to functionalize the reflectivesurface 90 for detecting the presence of chlorine (Cl—) ions in a liquidsolution. In another embodiment, the reflective surface 90 of the SPRmay be composed of titanium nitride (TiN), so that the sensing surface112 for the FET biomolecule sensor can detect the pH of a liquidsolution, the pH of the liquid solution then being correlated to theconcentration of protons (H⁺) in the liquid solution. In yet anotherembodiment, the surface of the reflective surface 90 of the SPR ischemically modified with proteins and/or ions for binding with proteinsand/or ions in the liquid solution in order to function as the sensingelement 112 of the FET biomolecule sensor. For example, to detectstrepavidin protein, the sensing surface 112 can be coated with biotin,because biotin specifically binds the streptavidin protein.

In each of the above examples, during measurement of the liquidsuspension 111 by the FET biomolecule sensor, charged bio molecules,e.g., chlorine (Cl⁻) and protons (H⁺), approach/adhere to the sensingsurface 112 of the FET biomolecule sensor, i.e., the reflective surface90 of the SPR, which changes the electrically properties of thebiomolecule sensor, such as the collector current (Ic).

FIGS. 7B and 8B depict another embodiment of the present disclosure inwhich the semiconductor device that is in electrical communication withthe reflective surface 90 of the SPR is a bipolar junction transistor(BJT) 300. The bipolar junction transistor (BJT) 300 that are depictedin FIGS. 7B and 8B includes an emitter region 301, base region 302 andcollector region 303. The bipolar junction transistor 300 that aredepicted in FIGS. 7B and 8B is similar to the biomolecule sensorprovided by the bipolar junction transistor (BJT) 100 that is describedabove with reference to FIGS. 1-6. Therefore, the above description ofthe BJT 100 that is depicted in FIGS. 1-3 is suitable for the BJT 300that is depicted in FIGS. 7B and 8B. For example, the description of theemitter region 10, the base region 15, and the collector region 20 thatare depicted in FIGS. 1 and 2, is suitable for the emitter region 301,base region 302 and collector region 303 of the BJT 300 that is depictedin FIGS. 7B and 8B. Further, the above description of the electricallyconductive contact 30 to the base region 15 for the BJT 100 describedabove with reference to FIGS. 1-6 is suitable for describing the sensingsurface of the BJT 300 that is depicted in FIGS. 7B and 8B, in whichsensing surface for the BJT 300 also provides the reflector surface 90of the SPR. Similar to the embodiments in which the semiconductor deviceis a FET, the sensing surface of the BJT may be an extended portion 312of the contact to the base region 302 of the BJT 300, or the sensingsurface for the BJT may be connected to the base region 302 of the BJT300 using a wired connection.

The sensors depicted in FIGS. 7A-8B, which combine SPR & FET sensingmethods, provides optical measurements of refractive index and mass ofthe sample, as provided by the SPR sensor, and electrical measurementsof electrical charge of the sample, as provided by the semiconductordevice, e.g., FET and/or BJT.

To provide the combined functions of a reflector surface 90 for the SPRdetector and a sensing surface for the semiconductor device, thereflector surface 90 may be a metal film having a thickness that is lessthan 150 nm. In some embodiments, the thickness of the metal film forthe reflector surface 90 of the SPR detector and the sensing surface forthe semiconductor device may range from 50 nm to 150 nm. In otherembodiments, the thickness of the metal film for the reflector surface90 of the SPR detector and the sensing surface for the semiconductordevice may range from 80 nm to 125 nm.

In prior SPR sensors, approximately 10% of the metal film that providesthe reflector surface 90 is in contact with the liquid solution 111whilst the rest of the area is occupied by the cell holding the fluid.The optical spot size is typically smaller than metal film surface area.In some embodiments of the present disclosure consistent with FIGS. 7Aand 8A, the extended gate FET sensor has a metal film (provided by thereflector surface 90) attached to the gate structure, wherein this metalfilm forms the sensing surface 112 for the FET biomolecule sensor. Theembodiments depicted in FIGS. 7A and 8A require that substantially theentire area of the sensing surface 112 for the FET biomolecule sensor bein contact with the liquid solution 111 from which the measurement istaken. A method has been proposed that successfully combines both SPR &FET sensing methods such that the sensing surface, i.e., reflectivesurface 90, simultaneously meets the criteria for both techniques andprovides unique information that would not be achieved through a singlemethod, i.e., SPR or semiconductor biomolecule sensor individually.

SPR sensing provides information about refractive index change at/nearthe solid liquid interface in the liquid solution sample, wherein therefractive index can be directly correlated to mass of solute within theliquid solution with strong binding ligands. Sensing occurs throughoutthe entire evanescent wave, in which the evanescent wave is much largerthan the dimension of biomolecules. In some embodiments, SPR providesthe total mass and allows determination of surface coverage, while thesemiconductor device sensing, e.g., FET or BJT sensor, providesinformation about the electrical environment. The semiconductor devicesensing typically occurs within the Debye length, wherein the Debyelength is smaller than the dimension of biomolecules in typical mediaused in liquid solution samples. The semiconductor device sensor, e.g.,FET or BJT sensor, typically gives the local charge bound to the sensingsurface, i.e., reflector surface 90.

Simultaneous SPR and semiconductor device sensors, e.g., FET and/or BJTsensors, can in principle provide complex information, such as molecularorientation at an interface (structure of bound species). Further, thepresence of interfacial charge is known to influence kinetics of DNAbinding and hybridization the latter of which can be correlated withbase pair mismatch. This type of configuration could be useful forcontrol & interpretation of molecular binding. Simultaneous detection byboth SPR and semiconductor sensor methods results in higher detectionaccuracy & fewer false positives. Simultaneous measurement may includerefractive index at the surface liquid solution sample by SPR, mass ofthe molecules in the at the interface by SPR and charges measured by thesemiconductor sensor, e.g., FET sensor or BJT sensor, on charged targetbio-molecules, e.g., proteins and DNA. Correlation of data provided bySPR and semiconductor sensors, e.g., FET sensor or BJT sensor, canprovide insight into adsorption/desorption of biomolecules from thesensing surface, as well as changes in protein conformation or othercharge target (e.g. DNA/RNA) configurations. Further, the simultaneousmeasurement can enable the measurement of changes in optical propertiesof the liquid solution sample at the interface as a function appliedvoltage to metal sensing surface of the semiconductor sensor, which isthe reflective surface 90 of the SPR sensor.

FIG. 7A depicts one embodiment of a combined semiconductor device, e.g.,biomolecule FET sensor, and surface plasmon resonance spectroscopy (SPR)based bio-sensor that employs a prism coupler 110. In this embodiment,the reflective surface 90 for the SPR sensor is smooth, as opposed tohaving a grating. In this embodiment, a reference electrode 400 isimmersed in the liquid solution 111, and a voltage (Vg) is applied toit. The sensing signal for the FET 200 is measured by measuring thedrain current (Id) flowing between source and drain in the thresholdregime, where |V_(g)|<V_(T), where V_(g) is the gate voltage applied togate electrode 209 and V_(T) is the threshold voltage. Whenbio-molecules attach to the sensing surface 112, i.e, reflectivestructure 90 of the SPR, charges on the molecules would cause thethreshold voltage (V_(T)) to change, which in turn causes the sensingdrain current to change. The sensing surface 112 of the FET sensor,which may also be the reflective surface 90 of the SPR, may be comprisedof a metal film. In the embodiment that is depicted in FIG. 7A, theentire sensing area for the FET sensor should be in contact with liquidsolution 111 being measured, and the metal film thickness should be lessthan 150 nm, e.g., approximately 50 nm.

Referring to FIG. 9, the optical spot size area 500 for taking the SPRmeasurements can be less than the sensing area 600 for the sensingsurface of the semiconductor device, e.g., FET and/or BJT semiconductordevice. There are many available choices for the metal of the sensingsurface, which includes but are not limited to gold, silver, and copper.In some embodiments, the dimensions of the sensing surface should beless than the dimensions of the fluid cell but greater than thedimensions of the light source projected on the sensor surface.

FIG. 8A depicts one embodiment of a combined semiconductor device, e.g.,biomolecule FET sensor, and surface plasmon resonance spectroscopy (SPR)based bio-sensor that employs a grating coupler. In the embodiment thatis depicted in FIG. 8A, surface plasmons are coupled using a metallicgrating. Grating coupled SPR may be employed with thicker films, e.g.,gold films, for the reflective surface 90 than the embodiments of thepresent disclosure using prism coupling, as depicted in FIG. 7A. Similarto the embodiment that is described above with reference to FIG. 7A, areference electrode 400 is immersed in the liquid solution 111, and avoltage (Vg) is applied to it. Sensing for the FET sensor depicted inFIG. 8A is similar to the previous configuration that is depicted inFIG. 7A.

FIG. 10 is a plot of the drain current (Id) measured as a function ofthe gate voltage (Vg) taken from a field effect transistor (FET)biomolecule sensor in an arrangement with an SPR sensor as depicted inFIGS. 7A-8B. The FET sensor includes a gold surface as an extended gatewhich provides the sensing surface of the FET sensor for detectingaptamers. Drain current (Id) is measured as a function of gate voltage(Vg) applied to solution before and after the self-assembly of aptamerson the gold surface. As depicted in FIG. 10, the drain current (Id)curve shifts when aptamers (affinity linkers) are attached to the goldsensing surface, in which the detection shift is towards rightindicating that aptamers are negatively charged. The aptamers areusually anchored to gold via thiol functionality. As more aptamers bindto the gold surface, the ID curves shift away from the curvecorresponding to the bare gold surface.

While the present disclosure has been particularly shown and describedwith respect to preferred embodiments thereof, it will be understood bythose skilled in the art that the foregoing and other changes in formsand details may be made without departing from the spirit and scope ofthe present disclosure. It is therefore intended that the presentdisclosure not be limited to the exact forms and details described andillustrated, but fall within the scope of the appended claims.

What is claimed is:
 1. A sensor in electrical communication with acontroller, the sensor comprising: a bipolar junction transistorincluding an emitter region, a base region, and a collector region; areservoir containing a solution, the reservoir positioned adjacent thebase region of the bipolar junction transistor; and a metal containingcontact extending from the base region into the reservoir, wherein themetal containing contact is configured to provide a sensing surface formeasuring at least one of presence of biomolecules in the solution,changing pH of the solution or a temperature of the solution.
 2. Thesensor of claim 1, wherein the emitter, base, and collector regions arearranged in a lateral orientation.
 3. The sensor of claim 1, wherein theemitter, base, and collector regions are arranged in a verticalorientation.
 4. The sensor of claim 1, wherein the metal containingcontact includes titanium nitride (TiN), a conducting metal coated witha thin layer of silver chloride (AgCl), silicon dioxide and/or otherinsulators, gold (Au), silver (Ag) or a metal and semiconductor alloythat supports a surface plasmon wave.
 5. The sensor of claim 1, whereinthe metal containing contact has a silver chloride surface, and changein collector current indicates a change in chloride concentration in thesolution, and changes in a subthreshold swing of the bipolar junctiontransistor indicates changes in the temperature of the solution.
 6. Thesensor of claim 1, wherein the metal containing contact includestitanium nitride (TiN), wherein the metal containing contact measures pHof the solution.
 7. The sensor of claim 1, wherein a first dielectricspacer is formed on an interface between the emitter region and the baseregion to electrically isolate the emitter region from the collectorregion.
 8. The sensor of claim 7, wherein a second dielectric spacer isformed on an interface between the base region and the collector regionto electrically isolate the emitter region from the collector region. 9.The sensor of claim 1, wherein the bipolar junction transistor isprogrammed by the controller to measure change in charge density inproximity to the metal containing contact, which is correlated to aconcentration of molecules of the solution contained within thereservoir.
 10. The sensor of claim 9, wherein the concentration ofmolecules are simultaneously measured by the bipolar junction transistorand a surface plasmon resonance (SPR) detector.